The kidney is an important organ that functions to maintain physical health by removing, by filtration, waste products, such as harmful or detrimental substances generated as a result of metabolic activity within a living organism, from the blood.
An example of a kidney disorder is kidney failure, and an example of a therapeutic method therefor is artificial dialysis. However, the burden imposed by medical expenses required for such therapeutic method is high, and thus the kidney failure is still a world-wide problem, not only from medical perspective, but also from medical economic aspect. Another example of a therapeutic method for kidney failure is renal transplantation, although shortage of donor organs is a serious issue of concern.
Meanwhile, pluripotent cells such as embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells), which can be obtained via introduction of undifferentiated cell-specific genes into somatic cells, have been reported (U.S. Pat. No. 5,843,780 and WO 2007/069666). As a therapeutic method for kidney failure, therefore, a therapeutic method that involves transplanting renal cells obtained by inducting differentiation of these pluripotent stem cells has been investigated. Moreover, development of therapeutic agents using homogeneous renal cells from these pluripotent stem cells is also under consideration.
The mammalian kidney is formed through three stages of development of the pronephros, the mesonephros, and the metanephros. Among these stages, the metanephros is known to be generated in the posterior region of the intermediate mesoderm. In this context, a method for inducing differentiation of mouse pluripotent stem cells into the intermediate mesoderm for nephrogenesis has been investigated (Mae, S. et al., 2010, Biochem. Biophys. Res. Commun., 393: 877-882). In addition, human pluripotent stem cells are successfully induced to differentiate into the intermediate mesoderm cells with the use of Activin A, Wnt, and BMP (International Application No. PCT/JP2011/067181 (WO 2012/011610)). Although such methods involving the use of growth factors are disadvantageous in terms of their very high cost, to date, no methods for inducing differentiation of human pluripotent stem cells into intermediate mesoderm cells without the use of growth factors have been reported.